Herpes simplex virus immediate-early protein ICP0 is targeted by SIAH-1 for proteasomal degradation.
J Virol
; 85(15): 7644-57, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21632771
ABSTRACT
Herpes simplex virus (HSV) immediate-early protein ICP0 is a transcriptional activator with E3 ubiquitin ligase activity that induces the degradation of ND10 proteins, including the promyelocytic leukemia protein (PML) and Sp100. Moreover, ICP0 has a role in the derepression of viral genomes and in the modulation of the host interferon response to virus infection. Here, we report that ICP0 interacts with SIAH-1, a cellular E3 ubiquitin ligase that is involved in multiple cellular pathways and is itself capable of mediating PML degradation. This novel virus-host interaction profoundly stabilized SIAH-1 and recruited this cellular E3 ligase into ICP0-containing nuclear bodies. Moreover, SIAH-1 mediated the polyubiquitination of HSV ICP0 in vitro and in vivo. After infection of SIAH-1 knockdown cells with HSV, higher levels of ICP0 were produced, ICP0 was less ubiquitinated, and the half-life of this multifunctional viral regulatory protein was increased. These results indicate an inhibitory role of SIAH-1 during lytic infection by targeting ICP0 for proteasomal degradation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Proteínas Imediatamente Precoces
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Ubiquitina-Proteína Ligases
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Complexo de Endopeptidases do Proteassoma
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article